Chronic Systemic Immune Dysfunction in African-Americans with Small Vessel-Type Ischemic Stroke

The incidence of small vessel-type (lacunar) ischemic strokes is greater in African-Americans compared to whites. The chronic inflammatory changes that result from lacunar stroke are poorly understood. To elucidate these changes, we measured serum inflammatory and thrombotic biomarkers in African-Americans at least 6 weeks post-stroke compared to control individuals. Cases were African-Americans with lacunar stroke (n = 30), and controls were age-matched African-Americans with no history of stroke or other major neurologic disease (n = 37). Blood was obtained \u3e 6 weeks post-stroke and was analyzed for inflammatory biomarkers. Freshly isolated peripheral blood mononuclear cells were stimulated with lipopolysaccharide (LPS) to assess immune responsiveness in a subset of cases (n = 5) and controls (n = 4). After adjustment for covariates, the pro-inflammatory biomarkers, soluble vascular cadherin adhesion molecule-1 (sVCAM-1) and thrombin anti-thrombin (TAT), were independently associated with lacunar stroke. Immune responsiveness to LPS challenge was abnormal in cases compared to controls. African-Americans with lacunar stroke had elevated blood levels of VCAM-1 and TAT and an abnormal response to acute immune challenge \u3e 6 weeks post-stroke, suggesting a chronically compromised systemic inflammatory response

A decision exercise to engage cancer patients and families in Deliberation about Medicare Coverage for advanced Cancer Care

BACKGROUND: Concerns about unsustainable costs in the US Medicare program loom as the number of retirees increase and experiences serious and costly illnesses like cancer. Engagement of stakeholders, particularly cancer patients and their families, in prioritizing insured services offers a valuable strategy for informing Medicare coverage policy. We designed and evaluated a decision exercise that allowed cancer patients and family members to choose Medicare benefits for advanced cancer patients. METHODS: The decision tool, Choosing Health plans All Together (CHAT) was modified to select services for advanced cancer patients. Patients with a cancer history (N = 246) and their family members (N = 194) from North Carolina participated in 70 CHAT sessions. Variables including participants’ socio-demographic characteristics, health status, assessments of the exercise and results of group benefit selections were collected. Routine descriptive statistics summarized participant characteristics and Fisher’s exact test compared group differences. Qualitative analysis of group discussions were used to ascertain reasons for or against selecting benefits. RESULTS: Patients and family members (N = 440) participated in 70 CHAT exercises. Many groups opted for such services as palliative care, nursing facilities, and services not currently covered by the Medicare program. In choosing among four levels of cancer treatment coverage, no groups chose basic coverage, 27 groups (39%) selected intermediate coverage, 39 groups (56%) selected high coverage, and 4 groups (6%) chose the most comprehensive cancer coverage. Reasons for or against benefit selection included fairness, necessity, need for prioritizing, personal experience, attention to family needs, holistic health outlook, preference for comfort, freedom of choice, and beliefs about the proper role of government. Participants found the exercise very easy (59%) or fairly easy (39%) to understand and very informative (66%) or fairly informative (31%). The majority agreed that the CHAT exercise led to fair decisions about priorities for coverage by which they could abide. CONCLUSIONS: It is possible to involve cancer patients and families in explicit discussions of their priorities for affordable advanced cancer care through the use of decision tools designed for this purpose. A key question is whether such a conversation is possible on a broader, national level

Cross-Calibration of Stroke Disability Measures: Bayesian Analysis of Longitudinal Ordinal Categorical Data Using Negative Dependence

It is common to assess disability of stroke patients using standardized scales, such as the Rankin Stroke Outcome Scale (RS) and the Barthel Index (BI). The Rankin Scale, which was designed for applications to stroke, is based on assessing directly the global conditions of a patient. The Barthel Index, which was designed for general applications, is based on a series of questions about the patient’s ability to carry out 10 basis activities of daily living. As both scales are commonly used, but few studies use both, translating between scales is important in gaining an overall understanding of the efficacy of alternative treatments, and in developing prognostic models that combine several data sets. The objective of our analysis is to provide a tool for translating between BI and RS. Specifically, we estimate the conditional probability distributions of each given the other. Subjects consisted of 459 individuals who sustained a stroke and who were recruited for the Kansas City Stroke Study from 1995 to 1998. Patients were assessed with BI and RS measures 1, 3 and 6 months after stroke. In addition, we included data from the Framingham study, in the form of cross-classifying patients by RS and coarsely aggregated BI. Our statistical estimation approach is motivated by several goals: (a) overcoming the difficulty presented by the fact that our two sources report data at different resolutions; (b) smoothing the empirical counts to provide estimates of probabilities in regions of the table that are sparsely population; (c) avoiding estimates that would conflict with medical knowledge about the relationship between the two measures and (d) estimating the relationship between RS and BI at three months after the stroke, while borrowing strength from measurements made at one and six months. We address these issues via a Bayesian analysis combining data augmentation and constrained semiparametric inference. Our results provide the basis for (a) comparing and integrating the results of clinical trials using different measures, and (b) integrating clinical trials results into comprehensive decision model for the assessment of long term implications and cost-effectiveness of stroke prevention and acute treatment interventions. In addition, our results indicate that the degree of agreement between the two measures is less strong than commonly reported, and emphasize the importance of trial designs that include multiple assessments of outcome

Dietary carbohydrate intake and high sensitivity C reactive protein in at-risk women and men

Background— The quality and quantity of dietary carbohydrate intake, measured as dietary glycemic load (GL), is associated with a number of cardiovascular disease (CVD) risk factors and, in healthy young women, is related to increased high sensitivity C-reactive protein (hsCRP) concentrations. Our objective was to determine if GL is related to hsCRP and other measures of CVD risk in a population of sedentary, overweight, dyslipidemic middle-aged women and men enrolled in an exercise intervention trial (STRRIDE). Methods— This was a cross-sectional evaluation of the relationships between measures of dietary carbohydrate intake, calculated from food frequency questionnaire data, and CVD risk factors, including plasma hsCRP, measured in 171 subjects. Results— After adjusting for energy intake, GL and other measures of carbohydrate intake were not independently related to hsCRP (P>0.05 for all). In analyses performed separately for each gender, only the quantity of carbohydrate intake was independently related to hsCRP (R2=0.28; P<0.04), and this relationship was present for women but not for men. The strongest relationship identified between GL and any CVD risk factor was for cardiorespiratory fitness (R2=0.12; P<0.02); an elevated GL was associated with a lower level of fitness in all subjects, and this relationship persisted even when the findings were adjusted for energy intake and gender (R2=0.48; P<0.03). Conclusions— In middle-aged, sedentary, overweight to mildly obese, dyslipidemic individuals, consuming a diet with a low GL is associated with better cardiorespiratory fitness. Our findings suggest that the current literature relating carbohydrate intake and hsCRP should be viewed with skepticism, especially in the extension to at-risk populations that include men. Originally published American Heart Journal, Vol. 154, No. 5, Nov 200

Introduction of the Tools for Economic Analysis of Patient Management Interventions in Heart Failure Costing Tool: A User-Friendly Spreadsheet Program to Estimate Costs of Providing Patient-Centered Interventions

Background—Patient-centered health care interventions, such as heart failure disease management programs, are under increasing pressure to demonstrate good value. Variability in costing methods and assumptions in economic evaluations of such interventions limit the comparability of cost estimates across studies. Valid cost estimation is critical to conducting economic evaluations and for program budgeting and reimbursement negotiations. Methods and Results—Using sound economic principles, we developed the Tools for Economic Analysis of Patient Management Interventions in Heart Failure (TEAM-HF) Costing Tool, a spreadsheet program that can be used by researchers and health care managers to systematically generate cost estimates for economic evaluations and to inform budgetary decisions. The tool guides users on data collection and cost assignment for associated personnel, facilities, equipment, supplies, patient incentives, miscellaneous items, and start-up activities. The tool generates estimates of total program costs, cost per patient, and cost per week and presents results using both standardized and customized unit costs for side-by-side comparisons. Results from pilot testing indicated that the tool was well-formatted, easy to use, and followed a logical order. Cost estimates of a 12-week exercise training program in patients with heart failure were generated with the costing tool and were found to be consistent with estimates published in a recent study. Conclusions—The TEAM-HF Costing Tool could prove to be a valuable resource for researchers and health care managers to generate comprehensive cost estimates of patient-centered interventions in heart failure or other conditions for conducting high-quality economic evaluations and making well-informed health care management decisions

Effects of exercise training alone vs a combined exercise and nutritional lifestyle intervention on glucose homeostasis in prediabetic individuals: a randomised controlled trial

Although the Diabetes Prevention Program (DPP) established lifestyle changes (diet, exercise and weight loss) as the ‘gold standard’ preventive therapy for diabetes, the relative contribution of exercise alone to the overall utility of the combined diet and exercise effect of DPP is unknown; furthermore, the optimal intensity of exercise for preventing progression to diabetes remains very controversial. To establish clinical efficacy, we undertook a study (2009 to 2013) to determine: how much of the effect on measures of glucose homeostasis of a 6 month programme modelled after the first 6 months of the DPP is due to exercise alone; whether moderate- or vigorous-intensity exercise is better for improving glucose homeostasis; and to what extent amount of exercise is a contributor to improving glucose control. The primary outcome was improvement in fasting plasma glucose, with improvement in plasma glucose AUC response to an OGTT as the major secondary outcome

Patient-Care Practices Associated with an Increased Prevalence of Hepatitis C Virus Infection among Chronic Hemodialysis Patients

Objective. To identify patient-care practices related to an increased prevalence of hepatitis C virus (HCV) infection among chronic hemodialysis patients. Design. Survey. Setting. Chronic hemodialysis facilities in the United States. Participants. Equal-probability 2-stage cluster sampling was used to select 87 facilities from all Medicare-approved providers treating 30–150 patients; 53 facilities and 2,933 of 3,680 eligible patients agreed to participate. Methods. Patients were tested for HCV antibody and HCV RNA. Data on patient-care practices were collected using direct observation. Results. The overall prevalence of HCV infection was 9.9% (95% confidence interval [CI], 8.2%–11.6%); only 2 of 294 HCV-positive patients were detected solely by HCV RNA testing. After adjusting for non-dialysis-related HCV risk factors, patient-care practices independently associated with a higher prevalence of HCV infection included reusing priming receptacles without disinfection (odds ratio [OR], 2.3 [95% CI, 1.4–3.9]), handling blood specimens adjacent to medications and clean supplies (OR, 2.2 [95% CI, 1.3–3.6]), and using mobile carts to deliver injectable medications (OR, 1.7 [95% CI, 1.0–2.8]). Independently related facility covariates were at least 10% patient HCV infection prevalence (OR, 3.0 [95% CI, 1.8–5.2]), patient-to-staff ratio of at least 7: 1 (OR, 2.4 [95% CI, 1.4–4.1]), and treatment duration of at least 2 years (OR, 2.4 [95% CI, 1.3–4.4]). Conclusions. This study provides the first epidemiologic evidence of associations between specific patient-care practices and higher HCV infection prevalence among hemodialysis patients. Staff should review practices to ensure that hemodialysis-specific infection control practices are being implemented, especially handling clean and contaminated items in separate areas, reusing items only if disinfected, and prohibiting mobile medication and clean supply carts within treatment areas

Exercise Training Amount and Intensity Effects on Metabolic Syndrome (From Studies of a Targeted Risk Reduction Intervention through Defined Exercise)

Although exercise improves individual risk factors of the metabolic syndrome (MS), there is little research on the effect of exercise on MS as a whole. The objective of this study was to determine how much exercise is recommended to reduce the prevalence of MS. Of 334 subjects randomized, 227 finished and 171 (80 women, 91 men) had complete data for all 5 Adult Treatment Panel III- defined MS risk factors and were included in this analysis. Subjects were randomly assigned to a six-month control or 1 of 3 eight-month exercise training groups: 1) low-amount/moderate-intensity (equivalent to walking ~19 km/week); 2) low-amount/vigorous-intensity (equivalent to jogging ~19 km/week); 3) high-amount/vigorous-intensity (equivalent to jogging ~32 km/week). The low- amount/moderate-intensity exercise prescription improved MS relative to inactive controls (p<0.05). However, the same amount of exercise at a vigorous intensity was not significantly better than inactive controls, suggesting that lower intensity exercise may be more effective in improving MS. The high-amount/vigorous-intensity group improved MS relative to controls (p<0.0001), the low- amount/vigorous-intensity group (p=0.001), and the moderate intensity group (p=0.07), suggesting an exercise dose effect. In conclusion, a modest amount of moderate intensity exercise, in the absence of dietary changes, significantly improved MS and thus supports the recommendation that adults get 30 minutes of moderate intensity exercise every day. A higher amount of vigorous exercise was shown to have greater and more widespread benefits. Finally, there is an indication that moderate intensity may be better than vigorous intensity exercise for improving MS. Originally published American Journal of Cardiology, Vol. 100, No. 12, Dec 200

Practical dyspnea assessment: relationship between the 0–10 numerical rating scale and the four-level categorical verbal descriptor scale of dyspnea intensity

Context—Measurement of dyspnea is important for clinical care and research. Objectives—To characterize the relationship between the 0–10 Numerical Rating Scale (NRS) and four-level categorical Verbal Descriptor Scale (VDS) for dyspnea assessment. Methods—This was a substudy of a double-blind randomized controlled trial comparing palliative oxygen to room air for relief of refractory breathlessness in patients with life-limiting illness. Dyspnea was assessed with both a 0–10 NRS and a four-level categorical VDS over the one-week trial. NRS and VDS responses were analyzed in cross section and longitudinally. Relationships between NRS and VDS responses were portrayed using descriptive statistics and visual representations. Results—Two hundred twenty-six participants contributed responses. At baseline, mild and moderate levels of breathlessness were reported by 41.9% and 44.6% of participants, respectively. NRS scores demonstrated increasing mean and median levels for increasing VDS intensity, from a mean (SD) of 0.6 (±1.04) for VDS none category to 8.2 (1.4) for VDS severe category. The Spearman correlation coefficient was strong at 0.78 (P < 0.0001). Based on the distribution of NRS scores within VDS categories, we calculated test characteristics of two different cutpoint models. Both models yielded 75% correct translations from NRS to VDS; however, Model A was more sensitive for moderate or greater dyspnea, with fewer misses downcoded. Conclusion—There is strong correlation between VDS and NRS measures for dyspnea. Proposed practical cutpoints for the relationship between the dyspnea VDS and NRS are 0 for none, 1–4 for mild, 5–8 for moderate, and 9–10 for severe

Impact of Hormone Replacement Therapy on Exercise Training-Induced Improvements in Insulin Action in Sedentary Overweight Adults

Exercise training (ET) and hormone replacement therapy (HRT) are both recognized influences on insulin action, but the influence of HRT on responses to ET has not been examined. In order to determine if HRT use provided additive benefits for the response of insulin action to ET, we evaluated the impact of HRT use on changes in insulin during the course of a randomized, controlled, aerobic ET intervention. Subjects at baseline were sedentary, dyslipidemic, and overweight. These individuals were randomized to six months of one of three aerobic ET interventions or continued physical inactivity. In 206 subjects, an insulin sensitivity index (SI) was obtained with a frequently sampled intravenous glucose tolerance test pre- and post-ET. Baseline and post-intervention fitness, regional adiposity, general adiposity, skeletal muscle biochemistry and histology, and serum lipoproteins were measured as other putative mediators influencing insulin action. Two-way analyses of variance were used to determine if gender or HRT use influenced responses to exercise training. Linear modeling was used to determine if predictors for response in SI differed by gender or HRT use. Women who used HRT (HRT+) demonstrated significantly greater improvements in SI with ET than women not using HRT (HRT-). In those HRT+ women, plasma triglyceride change best correlated with change in SI. For HRT- women, capillary density change, and for men, subcutaneous adiposity change, best correlated with change in SI. In summary, in an ET intervention, HRT use appears associated with more robust responses in insulin action. Also, relationships between ET induced changes in insulin action and potential mediators of change in insulin action are different for men, and for women on or off HRT. These findings have implications for the relative utility of ET for improving insulin action in middle-aged men and women, particularly in the setting of differences in HRT use. Address Originally published Metabolism, Vol. 57, No. 7, July 200